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Alogliptin After Acute Coronary Syndrome in Patients With Type 2 Diabetes
Study Questions:
What are the cardiovascular outcomes with alogliptin, a new inhibitor of dipeptidyl peptidase 4 (DPP-4), as compared with placebo in patients with type 2 diabetes (DM2) who had a recent acute coronary syndrome?
Methods:
The EXAMINE (Examination of Cardiovascular Outcomes With Alogliptin Versus Standard of Care) investigators randomly assigned patients with DM2 and either an acute myocardial infarction or unstable angina requiring hospitalization within the previous 15-90 days to receive alogliptin or placebo in addition to existing antihyperglycemic and cardiovascular drug therapy. The study design was a double-blind, noninferiority trial with a prespecified noninferiority margin of 1.3 for the hazard ratio for the primary endpoint of a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke.
Results:
A total of 5,380 patients underwent randomization and were followed for up to 40 months (median, 18 months). A primary endpoint event occurred in 305 patients assigned to alogliptin (11.3%) and in 316 patients assigned to placebo (11.8%) (hazard ratio, 0.96; upper boundary of the one-sided repeated confidence interval, 1.16; p < 0.001 for noninferiority). Glycated hemoglobin levels were significantly lower with alogliptin than with placebo (mean difference, −0.36 percentage points; p < 0.001). Incidences of hypoglycemia, cancer, pancreatitis, and initiation of dialysis were similar with alogliptin and placebo.
Conclusions:
The authors concluded that among patients with DM2 who had a recent acute coronary syndrome, the rates of major adverse cardiovascular events were not increased with the DPP-4 inhibitor alogliptin as compared with placebo.
Perspective:
This trial reported that treatment with alogliptin resulted in rates of major cardiovascular events that were similar to rates with placebo among patients with DM2 and substantial cardiovascular disease and cardiovascular risk. The similar rates of the primary endpoint in the alogliptin and placebo groups were observed in the context of modestly better glycemic control in patients who received alogliptin. Since the EXAMINE trial had a median duration of 18 months, the results do not rule out longer-term benefits or risks of alogliptin with respect to cardiovascular endpoints. This trial thus establishes the cardiovascular safety profile of alogliptin for use in patients with DM2 and even those with recent acute coronary syndrome, traditionally considered a high-risk group, and will help guide clinicians in choosing among the different antidiabetic agents when treating patients with DM2 and very high cardiovascular risk.
Keywords: Myocardial Infarction, Dipeptidyl Peptidase 4, Stroke, Neoplasms, Uracil, Acute Coronary Syndrome, Pancreatitis, Standard of Care, European Continental Ancestry Group, Diabetes Mellitus, Type 2, Risk Factors, Hypoglycemia, Glycated Hemoglobin A, Renal Dialysis, Piperidines, Blood Glucose, Hypoglycemic Agents, Confidence Intervals
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